title: Positron emission tomography/computed tomographic and magnetic resonance imaging in a murine model of progressive atherosclerosis using (64)Cu-labeled glycoprotein VI-Fc.
abstract: BACKGROUND
  Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using (64)Cu-labeled GPVI-Fc (fragment crystallized).
  
  
  RESULTS
  Four-week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6). Another group of WT mice received a ligation injury of the left carotid artery (n=6) or sham procedure (n=4). All mice received a total activity of ≈12 MBq (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron emission tomography using a NanoPET/computed tomographic scanner (Mediso, Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two hours after positron emission tomography/computed tomography, all mice were scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice, the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared with WT mice (ApoE(-/-): 13.2±1.5 Bq/cm(3) versus WT mice: 5.1±0.5 Bq/cm(3); P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid artery wall compared with the intact right carotid artery of WT mice and as a trend compared with sham procedure (injured: 20.7±1.3 Bq/cm(3) versus intact: 2.3±0.5 Bq/cm(3); P=0.028 versus sham: 12.7±1.7 Bq/cm(3); P=0.068). Results were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR contrast agent that measures plaque burden and vessel wall remodeling. Higher R1 relaxation rates were found in the injured carotid wall with a T1 mapping sequence (injured: 1.44±0.08 s(-1) versus intact: 0.91±0.02 s(-1); P=0.028 versus sham: 0.97±0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice compared with WT mice (ApoE(-/-): 1.49±0.05 s(-1) versus WT: 0.92±0.04 s(-1); P=0.028).
  
  
  CONCLUSIONS
  (64)Cu-GPVI-Fc positron emission tomographic imaging allows identification of exposed subendothelial collagen in injured WT and high-fat diet-fed ApoE(-/-) mice.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen.
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Alkystis
authors.initials: A
authors.lastname: Phinikaridou
authors.forename: Marcelo E
authors.initials: ME
authors.lastname: Andia
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Cooper
authors.forename: Andreas
authors.initials: A
authors.lastname: Schuster
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Griessinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurster
authors.forename: David
authors.initials: D
authors.lastname: Onthank
authors.forename: Martin
authors.initials: M
authors.lastname: Ungerer
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Eike
authors.initials: E
authors.lastname: Nagel
authors.forename: Rene M
authors.initials: RM
authors.lastname: Botnar
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D017536:Carotid Artery, Common; D003301:Copper Radioisotopes; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D003301:Copper Radioisotopes; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI
keywords: atherosclerosis; magnetic resonance imaging; positron-emission tomography and computed tomography